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Metabolic re-wiring of isogenic breast epithelial cell lines following epithelial to mesenchymal transition

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dc.contributor Háskóli Íslands
dc.contributor University of Iceland
dc.contributor.author Halldorsson, Skarphedinn
dc.contributor.author Rohatgi, Neha
dc.contributor.author Magnúsdóttir, Manuela
dc.contributor.author Choudhary, Kumari Sonal
dc.contributor.author Gudjonsson, Thorarinn
dc.contributor.author Knutsen, Erik
dc.contributor.author Barkovskaya, Anna
dc.contributor.author Hilmarsdóttir, Bylgja
dc.contributor.author Perander, Maria
dc.contributor.author Mælandsmo, Gunhild M.
dc.contributor.author Guðmundsson, Steinn
dc.contributor.author Rolfsson, Óttar
dc.date.accessioned 2018-03-02T12:35:39Z
dc.date.available 2018-03-02T12:35:39Z
dc.date.issued 2017-06
dc.identifier.citation Halldorsson, S., Rohatgi, N., Magnusdottir, M., Choudhary, K. S., Gudjonsson, T., Knutsen, E., . . . Rolfsson, Ó. (2017). Metabolic re-wiring of isogenic breast epithelial cell lines following epithelial to mesenchymal transition. Cancer Letters, 396, 117-129. doi:https://doi.org/10.1016/j.canlet.2017.03.019
dc.identifier.issn 0304-3835
dc.identifier.uri https://hdl.handle.net/20.500.11815/591
dc.description.abstract Epithelial to mesenchymal transition (EMT) has implications in tumor progression and metastasis. Metabolic alterations have been described in cancer development but studies focused on the metabolic re-wiring that takes place during EMT are still limited. We performed metabolomics profiling of a breast epithelial cell line and its EMT derived mesenchymal phenotype to create genome-scale metabolic models descriptive of both cell lines. Glycolysis and OXPHOS were higher in the epithelial phenotype while amino acid anaplerosis and fatty acid oxidation fueled the mesenchymal phenotype. Through comparative bioinformatics analysis, PPAR-γ1, PPAR- γ2 and AP-1 were found to be the most influential transcription factors associated with metabolic re-wiring. In silico gene essentiality analysis predicts that the LAT1 neutral amino acid transporter is essential for mesenchymal cell survival. Our results define metabolic traits that distinguish an EMT derived mesenchymal cell line from its epithelial progenitor and may have implications in cancer progression and metastasis. Furthermore, the tools presented here can aid in identifying critical metabolic nodes that may serve as therapeutic targets aiming to prevent EMT and inhibit metastatic dissemination.
dc.description.sponsorship Financial support for this work was provided by the Icelandic Research Council (Grants number: 130591-051, 130816-051 and 152358-051).
dc.format.extent 117-129
dc.language.iso en
dc.publisher Elsevier BV
dc.rights info:eu-repo/semantics/openAccess
dc.subject Cancer Research
dc.subject Oncology
dc.subject EMT
dc.subject Metabolism
dc.subject Genome scale models
dc.subject Breast cancer
dc.subject Krabbameinsrannsóknir
dc.subject Brjóstakrabbamein
dc.subject Efnaskipti
dc.subject Erfðafræði
dc.title Metabolic re-wiring of isogenic breast epithelial cell lines following epithelial to mesenchymal transition
dc.type info:eu-repo/semantics/article
dc.description.version Peer Reviewed
dc.identifier.journal Cancer Letters
dc.identifier.doi 10.1016/j.canlet.2017.03.019
dc.contributor.department Rannsóknarsetur í kerfislíffræði (HÍ)
dc.contributor.department Center for Systems Biology (UI)
dc.contributor.department Lífvísindasetur (HÍ)
dc.contributor.department Biomedical Center (UI)
dc.contributor.school Verkfræði- og náttúruvísindasvið (HÍ)
dc.contributor.school School of Engineering and Natural Sciences (UI)

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